Τόμος 24 (2010) – Τεύχος 3 – Άρθρο 4 – Επιθεώρηση Κλινικής Φαρμακολογίας και Φαρμακοκινητικής-Διεθνής Έκδοση – Volume 24 (2010) – Issue 3 – Article 4 – Epitheorese Klinikes Farmakologias και Farmakokinetikes-International Edition

Title Impact of various factors on drugs’ pharmacokinetics
Authors C. Tesseromatis1 and A. Alevizou2

1. Department of Pharmacology, Medical School, Kapodestrian University of Athens, Athens, Hellas

2. Department of Cardiothoracic Anaesthesia and Intensive Care, James Cook University Hospital, Marton Road, Middlesbrough TS4 3BW, UK

Citation Tesseromatis, C. and Alevizou, A.: Impact of various factors on drugs’ pharmacokinetics, Epitheorese Klin. Farmakol. Farmakokinet. 24(3): 259-264 (2010)
Publication Date Accepted for publication (Final Version): April 10, 2010
Full Text Language English
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Keywords Drugs, pharmacokinetics, factors.
Other Terms review article
Summary Pharmacokinetic properties of drugs are affected by many endogenous and exogenous factors. The extent of binding of drugs to plasma and tissues proteins is an important parameter for the total drug clinical assessment. Drugs with affinity for plasma proteins compete with other agents for the same protein binding site. The co-administration of acenocoumarin and certain antibiotics was found to prolong prothrombine time and increase antibiotics’ levels in rats. Increased cefalosporin levels were documented in hyperlipidaemic animals after co-administration of non-steroid anti-inflammatory drugs (NSAIDs). The presence of NSAIDs decreased the protein binding of clonidine both in intact and homogenized liver slices. Propranolol significantly decreases the binding process of lidocaine in liver tissue by displacing it from liver proteins. Diseases and generally stress conditions induce conformational changes either in plasma or in tissue protein affecting the binding of drugs in target molecules. Stress increased serum, tongue and liver lidocaine levels in experimental rats. In trauma or surgery the combination of antibiotics and NSAIDs enhanced the antibacterial drug concentration. In CCl4 induced liver disease an increase of animals’ serum, heart and liver propranolol level under lidocaine co-administration occurred. Circadian rhythm disruption, enhanced serum FFA levels in rats and decreased quinolone serum levels under UV light exposure. As a conclusion it should be noted that not all the changes in drug’s pharmacokinetics lead to adverse clinical effects, because there exist counterbalancing biological mechanisms and so attention should be given mainly to drugs with a narrow therapeutic index.
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